Tuesday, October 28, 2008

I hope what I am about to share is a sign of the times. It is very easy to wonder in this line of work--is all the action happening at the level of the leadership of the academic medical center or major organizations like AAMC? Is anything really changing in the trenches--or, as today's political jargon has it, down on Main Street?

I am a member of the American Academy of Family Physicians and as such am automatically enrolled as a member of the state and local chapters of AAFP. When I moved to Texas in 2006, I therefore became a member of the Texas and Galveston County chapters of AAFP. I did not attend meetings of the local chapter for two reasons. First, I was not involved in practice but rather in administration and teaching, and so had met very few of the local family docs. More important, I soon learned from the meeting notices that all their meetings were dinner meetings and were subsidized by drug reps. As a signatory to the No Free Lunch Pledge I could not attend (or at least would have to brown-bag it if I did).

I was therefore very intrigued to receive the notice below today (key point in italics, added):

The Galveston Chapter of the Texas Academy of Family Physicians invites you to:An Organizational MeetingThere is no educational program. We will have a round table discussion of the future of our chapter and the venue, frequency and format of meetings. Drug company sponsorship will probably go away.This is an important decision making meeting.Given that the new PhRMA code of conduct says that "modest" meals will continue as far as the drug companies are concerned, I am not sure exactly why the leadership of the society is certain that drug company sponsorship for meetings will disappear--unless it is because of the tightening of controls over not mixing up education with marketing, so that if CME credit is awarded for the educational presentation, then overt drug company sponsorship will not be allowed.

Nonetheless I pass along this anecdote as perhaps a hint that the times they are a-changin'.

Monday, October 20, 2008

Here's another complicated story that came to light (no pun intended) when some people noted that an entire issue of the Harvard Health Policy Review seemed to have disappeared from the web. One article in that issue was by Donald W. Light and Rebecca N. Warburton and accused the Harvard-based editors of the Journal of Health Economics (JHE) of bias in handling an earlier paper of theirs on the true costs of drug industry research. (Disclosure: I am currently involved with Don Light in co-authoring a couple of manuscripts.)

One of the most widely cited pair of papers, published in the JHE in 1991 and 2003, was by DiMasi et al. of the Tufts Center for the Study of Drug Development. The second paper reached the widely quoted conclusion that it costs the drug industry $800M to develop one new drug, when you count all the failed drugs that have to be investigated along the way. The Tufts center is well known to be funded almost entirely by the drug industry, and the $800M figure has been much repeated in industry-friendly sources.

Light and Warburton wrote a paper criticizing the methods used by DiMasi and colleagues, and also calling atention to how the funding of their center created a conflict of interest in relation to their research. They chose to submit the paper to JHE, on the natural assumption that the journal would find controversy about a previously published paper interesting to their readers.

The editorial board assigned editor Thomas McGuire to the Light-Warburton manuscript. Light and Warburton describe this as an editorial conflict of interest as McGuire had also edited the DiMasi papers and could view the Light-Warburton critique as an attack on his own editorial judgment. (I demur here and wonder if the paper was assigned to McGuire because drug company research might have been his own special area of expertise.)

There then followed a long soap opera of disputes between the authors and McGuire, which is painstakingly detailed in the second Light-Warburton article. Suffice it to say here that McGuire seemed more interested in excising from the manuscript any passage that might offend DiMasi and his Center, than in protecting the intellectual integrity of the exchange of ideas. McGuire also appeared to have sent the Light-Warburton manuscript to DiMasi for comment without notifying the authors of that fact. JHE accepted from DiMasi a long and tangential reply to the charges raised by Light and Warburton, and when the latter two tried to rebut statements in the reply, they found their own rebuttal severely restricted both in length and in content. Finally, when the paper was published on the web, Light and Warburton discovered for the first time that DiMasi and his colleagues had been allowed to append a further response, which they had never seen and to which they had no opportunity to reply. In short, rather than dealing seriously with the charges from Light and Warburton that DiMasi et al. had used inferior methods, JHE gave DiMasi et al. every possible opportunity to restate their own case and to impugn Light and Warburton in the process.

Irked by this evidence of extremely one-sided editorial management, Light and Warburton proceeded to write their paper #2 exposing the conduct of the JHE editors, contrasting their behavior unfavorably to several published codes of ethics for journal editors, and making recommendations for further reforms based on their own sad experience. Their paper #2 was published in the Harvard Health Policy Review, Spring 2008 issue. That entire issue has recently disappeared with no explanation from the periodical's website (according to several fellow Pharma bloggers--see for example the Oct. 20 post on http://www.gooznews.com/).

Sunday, October 19, 2008

What the AMA House of Delegates didn't have the guts, or the good sense, to do back in June, the Wisconsin Medical Society has now done, as noted by several of our fellow blogs. The core language of their recent statement to their members is:

Physicians shall accept no gifts from any provider of products that they prescribe to their patients such as personal items, office supplies, food, travel and time costs, or payment for participation in on-line CME. A complete ban eases the burdens of compliance, biased decision making, and patient distrust.The press release is dated Oct. 16 and can be found at http://www.wisconsinmedicalsociety.org/publications_and_media/press_releases

See how short and sweet it can be when you cut through the garbage and get straight to the point?

Pardon me while I wipe the egg off my face. I recently wrote about the spam comments that this blog had been attracting--that whenever I posted anything about Pfizer or certain key words, a comment would appear that seemed to be a blatant advertisement for their stop-smoking drug Chantix. I charged that the company must have a web-crawler program that was posting these comments automatically on all blogs.

An anonymous individual then appended a comment to that post, noting that the advertised website, which I had not bothered to click on, is not a Pfizer official website but actually a clever look-alike URL designed to make the viewer think it's Pfizer, but actually including a disclaimer in small print. In other words, this blog is being hacked into to advertise, but the people doing it are probably drug counterfeiters, not a legitimate drug company. "Don't you ever check facts?" asked this commentator, not unreasonably.

So I have taken down the original incorrect post and apologize to Pfizer and anyone else concerned. (I know by the way that this post will soon attract another phony "comment" from the web-crawler.)

Friday, October 17, 2008

The Healthy Skepticism listserv recently featured a very insightful and helpful comment from a Down Under pharmacist, Dr. Chris Doecke, of the Royal Adelaide Hospital. Though this blog is not primarily about why drugs cost so much, it is about techniques of drug marketing, so I thought Dr. Doecke's expose of the myths surrounding the term "biologicals" might be helpful to readers:

I also would like to highlight another very common myth that is often promoted in the area of new pharmaceuticals generally, but particularly with cancer treatments. Unfortunately many health professional have also been sucked in that most new drugs are "biologicals". Once said this somehow immediately justifies a $100K per year price tag without further challenge.

The quotes from the BW article were: "Because cancer treatments often consist of complex protein molecules that take years to develop, the drug multinationals left these risky products to small biotech ventures such as ImClone." "And Roche, bowing to pressure from Britain's National Institute for Health & Clinical Excellence (NICE), slashed the price of lung cancer drug Tarceva by $1,200 to $10,830 per four-month course of treatment."

Point one

Tarceva is erlotinib hydrochloride, a fairly simple small synthetic chemical. It is not a protein, it is not complex. It inhibits endogenous receptors in the body to modify physiologic processes (tyrosine kinase activity) just as atenolol inhibits endogenous receptors in the body (beta adrenergic receptors). Erlotinib is presented as a simple oral film coated tablet. We are being duped into linking these simple chemicals with "biologicals" because they are use for cancer treatment. Novartis did exactly the same with imatinib for CML. A$50-75K per year per patient for a simple oral dose form.

Point twoThe fact that a pharmaceutical is a proteins should NOT immediately justify a $100K per year price tag. Most are produced by using a recombinant process via a cell line. Once the process is established, cells simply spew out protein. I simplify a little, but as part of my PhD I produced active protein via recombinant techniques - hence isn't that difficult. Finally we have had recombinant human insulin available for decades at arguably reasonable prices.

In summary, this is a subtle process that we often get sucked into. That is, that everything for cancer is "biological" and that everything biological is rare, complex and expensive. As health practitioners we need to de-bunk these myths at every opportunity.

Thanks to Chris for giving permission to reprint his comment here, and he notes that he will be expanding the discussion for a future edition of the Healthy Skepticism Newsletter.

Tuesday, October 7, 2008

Following up on the previous post, in which I asked what would it take to change the culture of academic medicine so that a Nemeroff phenomenon would become impossible, I think it worth drilling down a bit deeper into the past record of Emory med school's relationship with its chair of psychiatry (who, it is now reported, has temporarily stepped down pending the promised new investigation). My text here is the previously cited NYT article: Gardiner Harris, "Top Psychiatrist Didn't Report Drug Makers' Pay," New York Times, Oct. 4, 2008 (see previous post for link).

Threaded through the account unearthed by Congressional investigators, showing a pattern of underreporting huge payments from drug companies and concealing financial conflicts of interest related to NIH grants, is a record of periodic and ineffectual efforts by Emory to rein in or at least get a grip on Dr. Nemeroff's behavior. Harris notes that in theory, if Nemeroff is found to have violated NIH reporting rules, Emory stands to lose $190M in NIH funding, assuming that the agency suspended all grants, which it hardly ever does.

Emory conducted an investigation of Nemeroff's outside consulting arrangements in 2004. A 14-page report mentioned "serious" and "significant" violations of university procedures regarding conflicts of interest. Harris states that Emory then did nothing in response to that report.

In 2006, Nemeroff had to resign as editor of Neuropsychopharmacology, after the journal published a paper with Nemeroff as first author without disclosing the financial relationship between Nemeroff and the maker of the medical device described glowingly in the paper. (Nemeroff claimed that this was due to a clerical error.) This led according to Harris to a "bitter e-mail exchange" between Nemeroff and an associate dean at Emory, Dr. Claudia Adkison, who referred to the published paper as "a piece of paid marketing."

In both 2004 and 2006, Emory's final concrete action regarding the charges against Nemeroff was to ask that he sign a letter stating that he did not accept more than $10,000 annually from any drug firm, thereby keeping within the NIH-specified limit. Nemeroff cheerfully kept signing all these letters, despite the fact that he was raking in more than $100,000 annually from several firms. (Indeed, Harris reports that he actually signed one such letter while at the Four Seasons Resort in Jackson Hole, where he earned $3000 of what would eventually amount to $170,000 that year from GlaxoSmithKline.) The Emory policy in short seems to have been "ask but don't expect him to tell, and since he didn't tell you, you can claim not to know anything."

The Emory statement in the wake of these new revelations, in addition to Nemeroff "voluntarily" stepping down as chair, is that the university is "working diligently to determine whether our policies have been observed consistently... Dr. Nemeroff has assured us that 'To the best of my knowledge, I have followed the appropriate university regulations concerning financial disclosures.'"

So naturally you might ask: how does it come to be that a chair of a department, who was shown by a university investigation four years ago to be untrustworthy in reporting financial conflicts of interest, is allowed simply to state on his own say-so that he has no conflicts, and the university meekly believes him? The answer may lie in an anonymous comment posted to this blog back in January when I first raised the Nemeroff issue. According to that respondent,who echoed a point of view I have heard from other academic psychiatrists, Nemeroff is pleased to bear the nickname "Boss of Bosses." He has a reputation for wielding tremendous power in psychiatry, especially taking advantage of his leverage with the big drug firms, and is ruthless in attacking those whom he doesn't like or who threaten him. One such event is described in some detail in HOOKED, the hiring and then subsequent firing of David Healy as head of a psychiatric research institute at the University of Toronto, due to Healy saying bad things about Prozac, whose manufacturer, Eli Lilly, was at the time considering a major grant to Toronto. Healy cheerfully sued Toronto and won, meaning that all the correspondence related to the firing is now in the public domain. In HOOKED I focused on Toronto's spineless behavior, but it is also interesting to note that almost certainly, Nemeroff was in the background pulling all the strings that led to Healy's dismissal.

Nemeroff was not shy about displaying his "Boss" side to his true bosses at Emory. He sent a confidential letter to the dean of the medical school at Emory in May 2000, listing the dozen corporate advisory boards in which he sat. He then ticked off the grants and endowments that those firms had paid to the Department of Psychiatry at Emory, and added, "Part of the rationale for [the companies'] funding our faculty in such a manner would be my service on those boards." Translation--you mess with my cozy relationships with these companies, and the industry gravy train to Emory dries up. The threat is only slightly veiled, that should Emory decide to take any serious action against Nemeroff for his unreported conflicts of interest, he could easily jump ship to a more permissive med school, taking a lot of his captive research faculty and all of his industry funding with him.

So now we come to the $64 question (or in Nemeroff's case, the $2.8M question), which is what has to happen to the medical school culture to not allow people like Nemeroff to have it all their own way. The incredibly optimistic answer is that universities and academic medical centers have to grow two pieces of anatomy, of which the one I can say in polite society is a backbone. They need to be willing to stand up to the blackmail and intimidation that a "Boss of Bosses" can throw their way--ideally cutting him off early in his career so that he never accumulates the incredible power that Nemeroff now seems to enjoy.

The more pessimistic answer is, what can you expect now that the post-Bayh-Dole university has declared its allegiance to making money over academic values? On this view, the conflict of interest train left the station a long time ago--some say, all the way back in 1980 when the Bayh-Dole act was passed (see HOOKED). If the university must make its research money from industry to stay afloat, then the unversity's conflict of interest is much bigger than any individual faculty member's conflict of interest, even Nemeroff's. And that assures that the university dare not bite the hand that feeds it, whether the hand is Nemeroff's or Eli Lilly's or GlaxoSmithKline's.

I have never met this person and for all I know he is a delightful human being. I bear him no personal ill will. The problem was that wherever I turned in my research on HOOKED, and the topic of conflicts of interest among academic physicians came up, Dr. Nemeroff seemed to be off the charts. He seemed to be the poster child for all that is wrong with the current cozy arrangements between Pharma and acadmic medicine. (Details in the post above.)

I wondered how it could be the case that Nemeroff seemed to be the Teflon Chair of Psychiatry just as Reagan had famously been the Teflon President--no charges ever stuck to him no matter how egregious the behavior--and was able to pursue his career as a leader of academic psychiatry despite all the embarrassing revelations (which apparently did not bother Emory University one whit).

Well, the stuff may now finally have hit the fan. Danny Carlat in his psychiatry blog:http://carlatpsychiatry.blogspot.com/, reporting on an article in the New York Times (http://www.nytimes.com/2008/10/04/health/policy/04drug.html?_r=3&hp&oref=slogin&oref=slogin&oref=slogin) as well as another in the Wall Street Journal, was soon followed by Integrity in Science Watch. The gist of the new exposes is that Nemeroff reported some tens of thousands of dollars in income from drug companies while in actuality he raked in millions. Specifically, according to Gardiner Harris in the Times, he made $2.8M from 2000-2007 and failed to report at least $1.2M, in the process violating Federal rules as principal investigator on studies for which he had a financial interest in the drug being tested. The new revelations come as a result of Congressional investigations, as part of Sens. Grassley and Kohl's proposal for sunshine legislation. Reportedly, as a result of these articles, Emory has belatedly decided that it needs to investigate Nemeroff.

What happens now will be a good test case for the future of the ethics of academic medicine. The basic issue is this. In today's world, a medical school like Emory looks at all the pluses and minuses of having a guy like Nemeroff as a powerful chair, and decides that the pluses outweigh the minuses. His publication record is stellar (mostly ghostwritten of course), he brings in huge research grants, and people in his specialty all over the world want to kiss the hem of his garments. What has to change, in the regulation and the culture of the academic medical center, so that it becomes a no-brainer that having a guy like this on your faculty is a net loser?